Long-term (12 h) incubation of NCB-20 neuroblastoma × Chinese hamster brain cell hybrid cells with phorbol dibutylate caused a decrease in the enzyme activity of protein kinase C (PKC). Under these conditions, the formation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and the mobilization of intracellular Ca2+ triggered by bradykinin (BK), were significantly increased. The alterations in BK-triggered membrane currents in the PKC down-regulated cells were also observed: enhancement of outward currents and decreased inward currents. These results strongly suggested that down-regulation of PKC enhanced BK-induced phosphoinositide metabolism by relieving from the negative feedback control operating between the receptor and phospholipase C, and that the increased Ca2+ responses due to accumulated Ins(1,4,5)P3 lead to enhanced outward currents.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Cell Biology